trying to sort out a confusion

[Guest guest]

Hi all

I think that there may be some confusion

about the recent discussion on “gene deletion”. I am posting, again - a very understandable email from Jeroen. Being a medic, he is able to explain things accurately but in

simpler terms for us non-medics.

I know that there are several other

doctors in this group. Perhaps they could step in and explain things a bit further?

Shireen Mohandes

London, England

> Sent: 11 November 2005 14:13

> blepharophimosis

> Subject: blepharophimosis Type I or

type II? Recent developments.

>

> Hi everybody,

>

> I read the recent posts about type I and type II BPES and

> infertility. I noticed that there are a lot of questions and

> uncertainties. Maybe I can clarify one and other. I have a

> degree in medicine and although I am now specializing in

> psychiatry, I am familiar with general medicine matters.

> Moreover, recently I spoke with Dr. Debaere, who's a world

> expert on genetic research in BPES.

>

> First I'd like to explain something about genetics. Humans

> have 46 chromosomes. We have 2 Sex chromosomes, XX (female)

> or XY (male), and 44 autosomal chromosomes. Each parent

> Passes 23 chromosomes (22 autosomal and 1 sex chromosome) so

> you get 23 chromosome " couples " .

> Chromosomes consist of DNA. Specific regions on chromosomes

> are called genes. There are a lot of genes (eye-colour,

> hair-colour, ...

> etc). In our cells there is a sophisticated system that can

> translate the information which is encoded in the DNA, the

> building material of genes, and form proteins. So a gene

> actually stands for a specific protein (like there is a gene

> for insulin). How do genetic disorders arise? Genetic

> disorders arise when there is a mutation (change) in the DNA

> within a specific gene region. This alters the gene and,

> thus, alters the protein which is formed. This is important.

> For example insulin which is different from normal insulin

> might not be able to lower blood sugar levels. Once a genetic

> disorder has arisen, which can happen spontaneously, it can

> be passed from parents to children. Genetic disorders can be

> " dominant " or " recessive " . When a genetic disorder is

> dominant only one of the two genes in the gene couple (the

> one from father or the one from mother) has to be altered to

> give rise to the disorder.

> When a genetic disorder is recessive both the father and the

> mother need to pass an altered gene to give rise to the disorder.

>

> What about BPES? BPES is an autosomal dominant genetic

> disorder. The gene is called FOXL2 and is located on

> chromosome 3. Chromosome 3 is an autosomal chromosome and the

> fact that the disorder is dominant means that you only need

> to have one altered gene to get the disorder. The different

> types (I and II) of BPES were first described in 1983

> (Zlotogora). Type I includes the four major features

> (blepharophimosis, ptosis, epicanthus inversus and

> telecanthus) and female infertility caused by premature

> ovarian failure (POF). Type II includes only the four major

> features. The difference between Type I and II is the

> position on which the DNA, and thus the gene, is mutated

> (altered). There are several (at least

> 21) known mutations of the FOXL2 gene. Depending on the

> location these mutations give rise to a shortened protein or

> an extended protein. The ones that give rise to a shortened

> protein cause type I and the ones that give rise to an

> extended protein cause type II.

> For some mutations it's not clear which type they cause.

> During a genetic investigation, which takes about three

> months, they try to find a known mutation to see if they are

> able to tell which type of BPES the affected person has.

>

> What about the management of POF? Management of POF needs to

> address the two major medical issues: hormone replacement

> therapy (HRT) and infertility.

>

> HRT: Oestrogen and progesterone replacement therapy is

> usually indicated. No comparative data are available to guide

> estrogen use in young women as most studies on HRT involve

> post-menopausal women, but the advantages often outweigh the

> possible side-effects.

>

> Infertility: No effective treatment for infertility exists.

> Adoption and oocyte (egg) donation are among the available

> options. However, more recently there are some new therapies

> under investigation.

> Ovarian tissue and oocyte cryopreservation (freezing in) hold

> promise for fertility preservation in the women most likely

> to undergo ovarian failure. Adolescent girls with BPES who

> have a risk of developing POF could be candidates for ovarian

> (not necessarily the complete ovary so it's not necessary to

> cause surgical

> menopause) cryopreservation. This cryopreserved ovarian

> tissue can be used in two ways: retransplanting and in vitro

> stimulation. The first live birth after retransplantation was

> reported in 2004 (this was not a woman with BPES). Note that

> these techniques are not (yet) applied on a large scale.

> Women with POF often reach menopause when they are 25-30 years old.

> In the old days, when women conceived at a younger age, this

> was not necessarily a problem. Nowadays most women start a

> career and think of children at an older age which makes POF

> more of an issue.

> Endocrinologic and gynecologic follow-up are advised in

> affected females in whom the BPES type is unknown or in whom

> BPES type I is suspected based on a positive family history

> or suggestive FOXL2 mutation.

>

> I myself had a blood sample taken one and a half month ago.

> We are planning to have more kids and we just want to know

> which type I have to be as prepared ad possible. I do not

> have the result yet. It takes about three months.

>

> I hope I was of any help. If some things are unclear please

> ask questions.

>

> Greetings,

> Jeroen.